RoL: Salivary proteome evolution as a framework to elucidate the mechanisms of functional change involving genomic structural variation

RoL：唾液蛋白质组进化作为阐明涉及基因组结构变异的功能变化机制的框架

• 批准号: 2049947
• 负责人: Omer Gokcumen
• 金额: $ 72.36万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2049947&HistoricalAwards=false
• 关键词: RoL; Salivary; proteome; evolution; framework

Evolution underlies the amazing diversity of life. Understanding the specific mechanisms through which evolution operates will help us to understand how new traits, abilities, and forms emerge. Saliva can serve as an ideal candidate for studying such evolutionary changes because it acts as the first interface for food, microorganisms, and other foreign molecules entering our bodies. This project will explore how new genes evolve and how they affect salivary function. It will do so by comparing the genetic variation, gene expression levels, and protein content of diverse mammalian species, focusing on salivary function. The results of this project will shed light on fundamental questions about how evolution operates, how new genes are formed, how their functions change over time, and why the properties of saliva vary so much among mammals. State-of-the-art approaches will be used and disseminated to a diverse group of graduate students from different institutions through hands-on workshops. Additionally, the research team’s efforts include hosting the annual Great Lakes Evolutionary Genomics Symposium, hosting more than 100 trainees and faculty interested in evolutionary genomics. The project will serve as a platform for the research team to engage with the public, promoting STEM training and evolutionary biology at both the national and international stage.The team’s recent work underlined the importance of particular types of genomic structural variants (SVs) in rapid salivary evolution. In this proposal, the research team will use innovative long-read sequencing-based approaches to generate de-novo assemblies and RNA sequences from the salivary glands of multiple mammalian species. Three hypotheses will be addressed: 1) Rapid gene turnover underlies the species-specific salivary proteome repertoires among mammals. 2) Gene duplications are a major mechanism through which protein dosage and function are fine-tuned in saliva. 3) Secreted proline-rich proteins are natural substrates for novel mucin formation through the expansion of subexonic repeats. This study will provide: 1) the most complete genomic and transcriptomic variation datasets for mammalian salivary glands; 2) a novel methodological framework where long-read sequencing data at the DNA and RNA levels will be integrated; and 3) a comprehensive database of specific genetic variations that will be of considerable evolutionary and biomedical significance for salivary phenotypes, such as lubrication of the oral cavity, breakdown of dietary starch, and host defense against pathogenic microorganisms.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

进化是生活中惊人的多样性的基础。了解进化操作将帮助我们了解新特征，能力和形式如何出现的特定机制。唾液可以作为研究这种进化变化的理想候选者，因为它是食物，微生物和其他进入我们身体的外国分子的第一个接口。该项目将探讨新基因的发展以及它们如何影响唾液功能。它可以通过比较哺乳动物种类的遗传变异，基因表达水平和蛋白质含量，重点是唾液功能。该项目的结果将阐明有关进化的运作方式，新基因的形成方式，其功能如何随时间变化以及为什么唾液的特性在哺乳动物中有很大变化的基本问题。最先进的方法将通过动手讲习班使用并传播给来自不同机构的一群研究生。此外，研究小组的努力包括举办年度大湖进化基因组学研讨会，主持100多名对进化基因组学有兴趣的学员和教师。该项目将成为研究团队与公众互动的平台，在国家和国际阶段促进STEM培训和进化生物学。该团队最近的工作强调了特定类型的基因组结构变体（SVS）在快速唾液进化中的重要性。在此提案中，研究团队将使用创新的基于长读测序的方法来生成多种哺乳动物物种唾液腺的De-Novo组件和RNA序列。将解决三个假设：1）哺乳动物中规格特异性的唾液蛋白质组库的快速基因转让。 2）基因复制是一种主要的机制，通过它在唾液中微调蛋白质剂量和功能。 3）分泌富含脯氨酸的蛋白是通过亚调子重复量扩展而形成新型Mutin的天然底物。这项研究将提供：1）哺乳动物唾液腺最完整的基因组和转录组变异数据集； 2）一种新颖的方法学框架，将整合在DNA和RNA水平上的长阅读测序数据； 3）一个特定遗传变异的综合数据库将是考虑唾液表型的进化和生物医学意义，例如口腔润滑，饮食淀粉的损坏以及对致病性微生物的托管防御的托管防御。这些奖项反映了NSF的法定责任和众多的依据，这是通过评估良好的依据，并具有广泛的依据。